Comprehensive analysis of the prognostic impact and immune implication of KIAA1429 in lung adenocarcinoma

Lei Guo; Qilin Huai; Bolun Zhou; Jianming Ying; Wei Guo

doi:10.1002/cai2.40

Comprehensive analysis of the prognostic impact and immune implication of KIAA1429 in lung adenocarcinoma

Cancer Innov. 2022 Dec 16;1(4):328-343. doi: 10.1002/cai2.40. eCollection 2022 Dec.

Authors

Lei Guo¹, Qilin Huai², Bolun Zhou², Jianming Ying¹, Wei Guo^{2

3}

Affiliations

¹ Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing The People's Republic of China.
² Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing The People's Republic of China.
³ Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer Chinese Academy of Medical Sciences Beijing The People's Republic of China.

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common lung cancer worldwide. N6-methyladenosine (m6A) methylation is a messenger RNA (mRNA) modification that plays a key role in tumor growth, immune microenvironment, and immunotherapy response. This study investigated the expression level, mutation status, prognostic value, and predictive ability for response to anti-PD-1 immunotherapy of the m6A methyltransferase KIAA1429 in LUAD.

Methods: This study examined multiple public data cohorts and independent samples from National Cancer Center (NCC) to evaluate the clinical significance and prognostic value of KIAA1429 in LUAD using bioinformatics techniques and immunohistochemical staining. We also evaluated the predictive value of KIAA1429 expression for anti-PD-1 immunotherapy efficacy. GSEA analysis was performed using KIAA1429 RNA-seq data at the tumor tissue level and cellular level to explore the potential molecular mechanism.

Results: In public databases, KIAA1429 was significantly associated with clinicopathological parameters in LUAD patients and had the potential to predict patient prognosis. The mutation characteristics of KIAA1429-related genes were analyzed and TP53, TTN, CSMD3, and other genes showed high mutation frequencies in LUAD. An independent cohort of 415 samples confirmed that high KIAA1429 expression was significantly associated with poorer prognosis in LUAD patients. Analysis of a small immunotherapy cohort showed that patients with high expression of KIAA1429 had better response after immunotherapy, and the proportion of patients with immunotherapy response was higher in this group.

Conclusions: Our study confirmed that KIAA1429 was highly expressed in LUAD and was significantly associated with poor prognosis. Moreover, KIAA1429 may serve as a potential marker to predict the efficacy of immunotherapy in LUAD.

Keywords: KIAA1429; immunotherapy; lung adenocarcinoma; m6A methylation; prognosis.